From context-dependence of mutations to molecular mechanisms of mutagenesis

Igor B. Rogozin, Boris A. Malyarchuk, Youri I Pavlov, Luciano Milanesi

Research output: Chapter in Book/Report/Conference proceedingConference contribution

11 Scopus citations

Abstract

Mutation frequencies vary significantly along nucleotide sequences such that mutations often concentrate at certain positions called hotspots. Mutation hotspots in DNA reflect intrinsic properties of the mutation process, such as sequence specificity, that manifests itself at the level of interaction between mutagens, DNA, and the action of the repair and replication machineries. The nucleotide sequence context of mutational hotspots is a fingerprint of interactions between DNA and repair/replication/modification enzymes, and the analysis of hotspot context provides evidence of such interactions. The hotspots might also reflect structural and functional features of the respective DNA sequences and provide information about natural selection. We discuss analysis of 8-oxoguanine- induced mutations in pro- and eukaryotic genes, polymorphic positions in the human mitochondrial DNA and mutations in the HIV-1 retrovirus. Comparative analysis of 8- oxoguanine-induced mutations and spontaneous mutation spectra suggested that a substantial fraction of spontaneous A*T->C*T mutations is caused by 8-oxoGTP in nucleotide pools. In the case of human mitochondrial DNA, significant differences between molecular mechanisms of mutations in hypervariable segments and coding part of DNA were detected. Analysis of mutations in the HIV-1 retrovirus suggested a complex interplay between molecular mechanisms of mutagenesis and natural selection.

Original languageEnglish (US)
Title of host publicationProceedings of the Pacific Symposium on Biocomputing 2005, PSB 2005
Pages409-420
Number of pages12
Publication statusPublished - Dec 1 2005
Event10th Pacific Symposium on Biocomputing, PSB 2005 - Big Island of Hawaii, United States
Duration: Jan 4 2005Jan 8 2005

Publication series

NameProceedings of the Pacific Symposium on Biocomputing 2005, PSB 2005

Conference

Conference10th Pacific Symposium on Biocomputing, PSB 2005
CountryUnited States
CityBig Island of Hawaii
Period1/4/051/8/05

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ASJC Scopus subject areas

  • Computational Theory and Mathematics
  • Biomedical Engineering

Cite this

Rogozin, I. B., Malyarchuk, B. A., Pavlov, Y. I., & Milanesi, L. (2005). From context-dependence of mutations to molecular mechanisms of mutagenesis. In Proceedings of the Pacific Symposium on Biocomputing 2005, PSB 2005 (pp. 409-420). (Proceedings of the Pacific Symposium on Biocomputing 2005, PSB 2005).